My lab uses biophysical techniques to unravel the dynamic personality of enzymes, signaling proteins, and the molecules they affect. We are particularly interested in the evolution of the impressive catalytic power of enzymes and the development of more complex signaling features in higher organisms. To shed light on these fundamental questions, we study modern and resurrected ancestral proteins with atomistic resolution by combining experiments and computation.
A key feature of life is change over time. In a search for how and why biological processes happen, my colleagues and I study, at the molecular level, changes of atomic coordinates in proteins over time. The ultimate goal is to “visualize” proteins at atomic resolution in real time as they function: enzymes during catalysis, signaling proteins in action, and proteins and drugs binding to their partners. To accomplish this, we use a variety of biophysical methods, including NMR (nuclear magnetic resonance) spectroscopy, X-ray crystallography, fast kinetics, single-molecule FRET (fluorescence resonance energy transfer), molecular dynamics simulations, bioinformatics, and other computational approaches. We then build the bridge from the microscopic dynamic behavior of individual proteins to the macroscopic dynamic behavior of biological function. Ultimately we employ the knowledge of protein dynamics for the design of novel highly efficient inhibitors.
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